Rapid identification of the NAT2 genotype in tuberculosis patients by multicolor melting curve analysis

Pharmacogenomics. 2016 Jul;17(11):1211-1218. doi: 10.2217/pgs-2016-0026. Epub 2016 Jul 5.

Abstract

Aim: NAT2 genotype is an indicator for isoniazid dosage adjusting for tuberculosis treatment. Multicolor melting curve analysis (MMCA) was evaluated as a potential method for NAT2 genotyping.

Materials & methods: 352 blood samples were analyzed by MMCA kit (Zeesan Biotech Co., Xiamen, China) targeting NAT2 SNPs at T341C, C481T, G590A and G857A, and direct sequencing was used as control.

Results: The sensitivity, specificity and accuracy of the MMCA assay for rapid NAT2 genotype detection were 97.9, 99.6 and 99.1% respectively, whereas for intermediate genotypes the values were 99.5, 98.7 and 99.1%, respectively, and for slow genotypes the values were 100% for the three aspects. The 24 saliva and blood for the control samples were also successfully analyzed using the MMCA assay, both produced uniform outcomes.

Conclusion: The MMCA assay described in our study is very promising for the efficient determination of NAT2 genotype, and can facilitate the personalized dosing of isoniazid.

Keywords: NAT2; acetylator genotype; multicolor melting curve analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Antitubercular Agents / administration & dosage
  • Antitubercular Agents / pharmacokinetics
  • Antitubercular Agents / therapeutic use
  • Arylamine N-Acetyltransferase / blood
  • Arylamine N-Acetyltransferase / genetics*
  • China
  • Genotype
  • Humans
  • Isoniazid / administration & dosage
  • Isoniazid / pharmacokinetics
  • Isoniazid / therapeutic use
  • Kinetics
  • Polymerase Chain Reaction / methods*
  • Polymorphism, Single Nucleotide / genetics
  • Precision Medicine
  • Saliva / chemistry
  • Sensitivity and Specificity
  • Tuberculosis / genetics*

Substances

  • Antitubercular Agents
  • Arylamine N-Acetyltransferase
  • NAT2 protein, human
  • Isoniazid